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Mechanisms of β- lactamase Inhibition and Heterotropic Allosteric Regulation of an Engineered β- lactamase-MBP Fusion Protein

Ke, Wei
http://rave.ohiolink.edu/etdc/view?acc_num=case1301692251

Abstract Details

2011, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
Expression of β-lactamases is the most common mechanisms of β-lactam antibiotic resistance clinically encountered. Both the numbers and types of β-lactamases are growing rapidly. Therefore, there is an urgent need to develop more potent antibiotics and β-lactamase inhibitors. My thesis work was focused on exploring the structural basis of β-lactamases overcoming new β-lactam antibiotics and inhibitors, on exploring this knowledge to develop improved inhibitors, and on exploring other ways of regulation (molecular switch). The SHV-1 β-lactamase, KPC-2 carbapenemase and inhibitor-resistant S130G SHV will be used as the model system to characterize the active site chemistry of enzyme-inhibitor complexes. Three types of inhibitors were tested including the ones exploiting the function of R1 substituent, exploiting the function of R2 substituent, and exploiting transition state inhibitors. Also TEM-MBP fusion protein will be used to investigate the mechanisms of heterotropic allosteric regulation.
Paul Carey (Committee Chair)
Robert Bonomo (Committee Member)
Menachem Shoham (Committee Member)
Marion Skalweit (Committee Member)
Focco van den Akker (Advisor)
198 p.
Biochemistry
&946; -lactamase,antibiotic resistance, &946; -lactamase inhibitor, allosteric

Recommended Citations

Citations

  • Ke, W. (2011). Mechanisms of β- lactamase Inhibition and Heterotropic Allosteric Regulation of an Engineered β- lactamase-MBP Fusion Protein [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1301692251

    APA Style (7th edition)

  • Ke, Wei. Mechanisms of β- lactamase Inhibition and Heterotropic Allosteric Regulation of an Engineered β- lactamase-MBP Fusion Protein. 2011. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1301692251.

    MLA Style (8th edition)

  • Ke, Wei. "Mechanisms of β- lactamase Inhibition and Heterotropic Allosteric Regulation of an Engineered β- lactamase-MBP Fusion Protein." Doctoral dissertation, Case Western Reserve University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1301692251

    Chicago Manual of Style (17th edition)

case1301692251
1,101
© 2011, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.